A multivalent vaccine for Staphylococcus aureus

金黄色葡萄球菌多价疫苗

• 批准号: 10515340
• 负责人: JON OSCHERWITZ
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10515340
• 关键词: Adjuvant; Aerosols; Amino Acids; Antibodies; Antigens; Bacillus anthracis; Bacteria; Bacterial Endocarditis; Biological Assay; Chickenpox; Clinical Trials; Communicable Diseases; Communities; Cytolysins; Cytotoxin; Data; Development; Disease; Enabling Factors; Epitopes; Evaluation; Gram-Positive Bacteria; Growth; HIV-1; Hemolysin; Hepatitis; Hospitals; Host Defense; Human; Humoral Immunities; Immune Sera; Immunity; Immunization; In Vitro; Infection; Infectious Skin Diseases; Malaria; Mediating; Medical; Methicillin Resistance; Modeling; Molecular; Monoclonal Antibodies; Morbidity - disease rate; Mus; Oryctolagus cuniculus; Panton-Valentine leukocidin; Performance; Pertussis; Phase; Pneumonia; Poliomyelitis; Production; Public Health; Reproduction spores; Sepsis; Services; Skin injury; Specificity; Staphylococcal Vaccines; Staphylococcus aureus; Staphylococcus aureus infection; Superantigens; Toxin; United States; Vaccination; Vaccines; Validation; Vancomycin; Virulence; Virulence Factors; Virulent; Virus-like particle; Vulnerable Populations; Work; alpha Toxin; cross reactivity; cytotoxicity; design; economic impact; efficacy evaluation; human disease; immunogenic; leukotoxin; lung injury; member; methicillin resistant Staphylococcus aureus; military veteran; mortality; mouse model; nanoparticle; neutralizing antibody; pathogen; prevent; protective efficacy; prototype; resistant strain; response; success; tissue injury; vaccine failure; vaccine trial

Staphylococcus aureus is a gram positive bacteria that possesses a multitude of virulence factors. It is a frequent and severe pathogen in hospitals and of increasing concern in the community, where it results in severe skin infections, pneumonia, sepsis and lethal bacterial endocarditis. A significant proportion of these infections are the result of methicillin-resistant S. aureus (MRSA). We have developed a highly immunogenic prototype nanoparticle vaccine capable of rapidly eliciting antibody against the pore neutralizing determinant (PND) within alpha toxin (AT), a ubiquitous and critical virulence factor of MRSA. Previous work has demonstrated that Ab against the PND is highly efficacious in preventing tissue injury and bacterial growth in a rigorous mouse dermonecrosis model, and in protecting mice in a lethal model of S. aureus pneumonia. In this project, we will utilize the human hepatitis core antigen platform to develop nanoparticle vaccines capable of neutralizing the key leukotoxins including gamma toxin, Panton Valentine leukocidin, LukED and LukGH, which are critical, secreted virulence factors which enable S. aureus to evade host immunity, and a nanoparticle vaccine targeting the previously validated PND of AT. The vaccines emerging from these studies will be uniquely effective against MRSA infections and will ideally be the basis of an efficacious, multivalent nanoparticle vaccine for MRSA.

金黄色葡萄球菌是一种革兰氏阳性菌，具有多种毒力 因素它是医院中常见和严重的病原体， 社区，在那里它会导致严重的皮肤感染，肺炎，败血症和致命的 细菌性心内膜炎这些感染中有很大一部分是由于 耐甲氧西林表皮葡萄金黄色葡萄球菌（MRSA）。我们研制出了一种免疫原性很强的 能够快速引发针对孔的抗体的原型纳米颗粒疫苗 α毒素（AT）中的中和决定簇（PND），是一种普遍存在的关键性的 MRSA毒力因子以前的工作已经证明，抗PND的Ab是 在严格的小鼠中高度有效地防止组织损伤和细菌生长 皮肤坏死模型，并在S.金黄色肺炎 本项目将利用人肝炎核心抗原平台， 能够中和关键白细胞毒素的纳米颗粒疫苗 毒素，Panton Valentine杀白细胞素，LukED和LukGH，这是关键的，分泌 使S.金黄色葡萄球菌逃避宿主免疫， 靶向先前验证的AT PND的疫苗。疫苗的出现， 这些研究将是唯一有效的抗MRSA感染， 为MRSA的有效多价纳米颗粒疫苗奠定了基础。